1. Field of the Invention
The invention relates to polycyclic nucleotide guanine phosphodiesterase V inhibitors.
2. Description of Related Art
Phosphodiesterase (“PDE”) V inhibitor compounds are described by Kenneth J. Murray in Phosphodiesterase VA Inhibitors, DN & P 6(3), pp. 150-156 (April, 1993), which is hereby incorporated herein by reference in its entirety, to have potential therapeutic value for a number of physiological disorders. One compound disclosed in the Murray article is MIMAX, a polycyclic xanthine PDE V inhibitor substituted at its 8-position with a —NHCH3 group. U.S. Pat. No. 5,409,934, U.S. Pat. No. 5,470,579, WO 93/23401, WO 92/05176 and WO 92/05175, each of which is hereby incorporated herein by reference in its entirety, disclose a series of xanthine PDE V inhibitors that are substituted at the 8-position with a number of different functionalities. Other types of heterocyclic PDE V inhibitors useful for treating impotence are disclosed in U.S. Pat. No. 6,140,329, U.S. Pat. No. 6,100,270 and WO 94/28902, all of which are hereby incorporated herein by reference in their entirety.
Specific PDE V inhibitors have been found useful for specific indications. For example, the use of specific PDE V inhibitors for treating impotence has met with commercial success with the introduction of sildenafil citrate, a PDE V inhibitor better known as Viagra® (Pfizer, NY, N.Y.). The chemistry and use of Viagra®, including its mechanism of action in treating erectile dysfunction, are taught in EP 0 702 555 B1. Additional PDE V inhibitors useful for treating erectile dysfunction are disclosed in WO 99/24433.
Erectile dysfunction is a treatable and highly recognized health concern, affecting more than 30 million men in the United States, including one in four over age 65. Erectile dysfunction occurs when a man consistently is unable to sustain an erection sufficient for conducting sexual intercourse. In the past, psychological reasons were the most common explanation for erectile dysfunction or it was considered a natural part of aging. However, researchers today acknowledge that more than 70 percent of instances of erectile dysfunction are due to physical or medical problems. There are several factors that may contribute to erectile dysfunction, including:                Poor blood circulation—atherosclerosis or hardening of the arteries, high blood pressure and high cholesterol.        Neurological disorders—multiple sclerosis, Alzheimer's disease and Parkinson's disease.        Hormone imbalances—diabetes, thyroid disorders and low testosterone levels.        Trauma—spinal cord injury, prostate surgery or other trauma to the pelvic area.        Prescription and over-the-counter medications—blood pressure medications, antidepressants and certain drug combinations.        Lifestyle habits—smoking, alcohol and other drugs.        
U.S. Pat. No. 5,939,419 and U.S. Pat. No. 5,393,755, both of which are hereby incorporated herein by reference in their entirety, disclose polycyclic guanine PDE V derivatives that are useful for the treatment of cardiovascular and pulmonary disorders.
As has been shown by the representative art, certain xanthine/guanine PDE V inhibitors have been found to be useful for treating cardiovascular and pulmonary disorders, while others have been found useful for treating impotence.
It is an object of the invention to provide a polycyclic guanine PDE V inhibitor that possesses one or more of the following: beneficial therapeutic properties, useful pharmacological properties and good metabolic stability.
It is another object of the invention to provide a polycyclic guanine PDE V inhibitor that is effective for treating a variety of physiological symptoms and diseases in which PDE V plays a role.
It is still another object of invention to provide a polycyclic guanine PDE V inhibitor that is highly potent and selective over other types of PDEs.
It is also an object of the invention to provide a polycyclic guanine PDE V inhibitor that is especially effective for treating erectile dysfunction with minimal side effects.
These and other objects of the invention will become apparent as the description progresses.